Devices for controlling high frequency spinal cord modulation for inhibiting pain, and associated systems and methods, including simplified controllers

ABSTRACT

Selective high-frequency spinal chord modulation for inhibiting pain with reduced side affects and associated systems and methods are disclosed. In particular embodiments, high-frequency modulation in the range of from about 1.5 KHz to about 50 KHz may be applied to the patient&#39;s spinal chord region to address low back pain without creating unwanted sensory and/or motor side affects. In other embodiments, modulation in accordance with similar parameters can be applied to other spinal or peripheral locations to address other indications. In particular embodiments, aspects of the foregoing modulation therapies may be implemented by systems and devices that have simplified functionalities.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application claims priority to U.S. Provisional ApplicationNo. 61/176,868, filed May 8, 2009 and incorporated herein by reference.The present application claims priority to U.S. Provisional ApplicationNo. 61/171,790, filed Apr. 22, 2009 and incorporated herein byreference.

TECHNICAL FIELD

The present disclosure is directed generally to devices for controllinghigh frequency spinal cord modulation for inhibiting pain, andassociated systems and methods, including simplified controllers.

BACKGROUND

Neurological stimulators have been developed to treat pain, movementdisorders, functional disorders, spasticity, cancer, cardiac disorders,and various other medical conditions. Implantable neurologicalstimulation systems generally have an implantable pulse generator andone or more leads that deliver electrical pulses to neurological tissueor muscle tissue. For example, several neurological stimulation systemsfor spinal cord stimulation (SCS) have cylindrical leads that include alead body with a circular cross-sectional shape and one or moreconductive rings spaced apart from each other at the distal end of thelead body. The conductive rings operate as individual electrodes and, inmany cases, the SCS leads are implanted percutaneously through a largeneedle inserted into the epidural space, with or without the assistanceof a stylet.

Once implanted, the pulse generator applies electrical pulses to theelectrodes, which in turn modify the function of the patient's nervoussystem, such as by altering the patient's responsiveness to sensorystimuli and/or altering the patient's motor-circuit output. In paintreatment, the pulse generator applies electrical pulses to theelectrodes, which in turn can generate sensations that mask or otherwisealter the patient's sensation of pain. For example, in many cases,patients report a tingling or paresthesia that is perceived as morepleasant and/or less uncomfortable than the underlying pain sensation.While this may be the case for many patients, many other patients mayreport less beneficial effects and/or results. Accordingly, thereremains a need for improved techniques and systems for addressingpatient pain.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is a partially schematic illustration of an implantable spinalcord modulation system positioned at the spine to deliver therapeuticsignals in accordance with several embodiments of the presentdisclosure.

FIG. 1B is a partially schematic, cross-sectional illustration of apatient's spine, illustrating representative locations for implantedlead bodies in accordance with embodiments of the disclosure.

FIG. 2 is a bar chart illustrating pain reduction levels for patientsover a four day period of a clinical study, during which the patientsreceived therapy in accordance with an embodiment of the disclosure, ascompared with baseline levels and levels achieved with conventionalspinal cord stimulation devices.

FIG. 3 is a bar chart comparing the number of times patients receivingtherapy in accordance with an embodiment of the present disclosureduring a clinical study initiated modulation changes, as compared withsimilar data for patients receiving conventional spinal cordstimulation.

FIG. 4 is a bar chart illustrating activity performance improvements forpatients receiving therapy in accordance with an embodiment of thedisclosure, obtained during a clinical study.

FIG. 5A is a bar chart comparing activity performance levels forpatients performing a variety of activities, obtained during a clinicalstudy.

FIGS. 5B and 5C are bar charts illustrating sleep improvement forpatients receiving therapy in accordance with embodiments of thedisclosure, obtained during a clinical study.

FIG. 6A is a bar chart illustrating successful therapy outcomes as afunction of modulation location for patients receiving therapy inaccordance with an embodiment of the disclosure, obtained during aclinical study.

FIGS. 6B and 6C are flow diagrams illustrating methods conducted inaccordance with embodiments of the disclosure.

FIG. 7A illustrates an arrangement of leads used during a follow-onclinical study in accordance with an embodiment of the disclosure.

FIG. 7B illustrates results obtained from a follow-on clinical study ofpatients receiving therapy in accordance with an embodiment of thedisclosure.

FIG. 8 is a schematic illustration identifying possible mechanisms ofaction for therapies in accordance with the present disclosure, ascompared with an expected mechanism of action for conventional spinalchord stimulation.

FIG. 9 is a partially schematic illustration of a lead body configuredin accordance with an embodiment of the disclosure.

FIGS. 10A-10C are partially schematic illustrations of extendible leadsconfigured in accordance with several embodiments of the disclosure.

FIGS. 11A-11C are partially schematic illustrations of multifilar leadsconfigured in accordance with several embodiments of the disclosure.

FIGS. 12A-12B illustrate patient-operated remote control devices inaccordance with particular embodiments of the disclosure.

FIGS. 13A-13E illustrate practitioner-operated devices in accordancewith particular embodiments of the disclosure.

DETAILED DESCRIPTION 1.0 Introduction

The present technology is directed generally to spinal cord modulationand associated systems and methods for inhibiting pain via waveformswith high frequency elements or components (e.g., portions having highfundamental frequencies), generally with reduced or eliminated sideeffects. Such side effects can include unwanted motor stimulation orblocking, and/or interference with sensory functions other than thetargeted pain. Several embodiments also provide simplified spinal cordmodulation systems and components, and simplified procedures for thepractitioner and/or the patient. Specific details of certain embodimentsof the disclosure are described below with reference to methods formodulating one or more target neural populations (e.g., nerves) or sitesof a patient, and associated implantable structures for providing themodulation. Although selected embodiments are described below withreference to modulating the dorsal column, dorsal horn, dorsal root,dorsal root entry zone, and/or other particular regions of the spinalcolumn to control pain, the modulation may in some instances be directedto other neurological structures and/or target neural populations of thespinal cord and/or other neurological tissues. Some embodiments can haveconfigurations, components or procedures different than those describedin this section, and other embodiments may eliminate particularcomponents or procedures. A person of ordinary skill in the relevantart, therefore, will understand that the disclosure may include otherembodiments with additional elements, and/or may include otherembodiments without several of the features shown and described belowwith reference to FIGS. 1A-13E.

In general terms, aspects of many of the following embodiments aredirected to producing a therapeutic effect that includes pain reductionin the patient. The therapeutic effect can be produced by inhibiting,suppressing, downregulating, blocking, preventing, or otherwisemodulating the activity of the affected neural population. In manyembodiments of the presently disclosed techniques, therapy-inducedparesthesia is not a prerequisite to achieving pain reduction, unlikestandard SCS techniques. It is expected that the techniques describedbelow with reference to FIGS. 1A-13E can produce more effective, morerobust, less complicated and/or otherwise more desirable results thancan existing spinal cord stimulation therapies.

FIG. 1A schematically illustrates a representative treatment system 100for providing relief from chronic pain and/or other conditions, arrangedrelative to the general anatomy of a patient's spinal cord 191. Thesystem 100 can include a pulse generator 101, which may be implantedsubcutaneously within a patient 190 and coupled to a signal deliveryelement 110. In a representative example, the signal delivery element110 includes a lead or lead body 111 that carries features fordelivering therapy to the patient 190 after implantation. The pulsegenerator 101 can be connected directly to the lead 111, or it can becoupled to the lead 111 via a communication link 102 (e.g., anextension). Accordingly, the lead 111 can include a terminal sectionthat is releasably connected to an extension at a break 114 (shownschematically in FIG. 1A). This allows a single type of terminal sectionto be used with patients of different body types (e.g., differentheights). As used herein, the terms lead and lead body include any of anumber of suitable substrates and/or support members that carry devicesfor providing therapy signals to the patient 190. For example, the lead111 can include one or more electrodes or electrical contacts thatdirect electrical signals into the patient's tissue, such as to providefor patient relief. In other embodiments, the signal delivery element110 can include devices other than a lead body (e.g., a paddle) thatalso direct electrical signals and/or other types of signals to thepatient 190.

The pulse generator 101 can transmit signals (e.g., electrical signals)to the signal delivery element 110 that up-regulate (e.g., stimulate orexcite) and/or down-regulate (e.g., block or suppress) target nerves. Asused herein, and unless otherwise noted, the terms “modulate” and“modulation” refer generally to signals that have either type of theforegoing effects on the target nerves. The pulse generator 101 caninclude a machine-readable (e.g., computer-readable) medium containinginstructions for generating and transmitting suitable therapy signals.The pulse generator 101 and/or other elements of the system 100 caninclude one or more processors 107, memories 108 and/or input/outputdevices. Accordingly, the process of providing modulation signals andexecuting other associated functions can be performed bycomputer-executable instructions contained on computer-readable media,e.g., at the processor(s) 107 and/or memory(s) 108. The pulse generator101 can include multiple portions, elements, and/or subsystems (e.g.,for directing signals in accordance with multiple signal deliveryparameters), housed in a single housing, as shown in FIG. 1A, or inmultiple housings.

The pulse generator 101 can also receive and respond to an input signalreceived from one or more sources. The input signals can direct orinfluence the manner in which the therapy instructions are selected,executed, updated and/or otherwise performed. The input signal can bereceived from one or more sensors 112 (one is shown schematically inFIG. 1 for purposes of illustration) that are carried by the pulsegenerator 101 and/or distributed outside the pulse generator 101 (e.g.,at other patient locations) while still communicating with the pulsegenerator 101. The sensors 112 can provide inputs that depend on orreflect patient state (e.g., patient position, patient posture and/orpatient activity level), and/or inputs that are patient-independent(e.g., time). In other embodiments, inputs can be provided by thepatient and/or the practitioner, as described in further detail later.Still further details are included in co-pending U.S. application Ser.No. 12/703,683, filed on Feb. 10, 2010 and incorporated herein byreference.

In some embodiments, the pulse generator 101 can obtain power togenerate the therapy signals from an external power source 103. Theexternal power source 103 can transmit power to the implanted pulsegenerator 101 using electromagnetic induction (e.g., RF signals). Forexample, the external power source 103 can include an external coil 104that communicates with a corresponding internal coil (not shown) withinthe implantable pulse generator 101. The external power source 103 canbe portable for ease of use.

In another embodiment, the pulse generator 101 can obtain the power togenerate therapy signals from an internal power source, in addition toor in lieu of the external power source 103. For example, the implantedpulse generator 101 can include a non-rechargeable battery or arechargeable battery to provide such power. When the internal powersource includes a rechargeable battery, the external power source 103can be used to recharge the battery. The external power source 103 canin turn be recharged from a suitable power source (e.g., conventionalwall power).

In some cases, an external programmer 105 (e.g., a trial modulator) canbe coupled to the signal delivery element 110 during an initial implantprocedure, prior to implanting the pulse generator 101. For example, apractitioner (e.g., a physician and/or a company representative) can usethe external programmer 105 to vary the modulation parameters providedto the signal delivery element 110 in real time, and select optimal orparticularly efficacious parameters. These parameters can include theposition of the signal delivery element 110, as well as thecharacteristics of the electrical signals provided to the signaldelivery element 110. In a typical process, the practitioner uses acable assembly 120 to temporarily connect the external programmer 105 tothe signal delivery device 110. The cable assembly 120 can accordinglyinclude a first connector 121 that is releasably connected to theexternal programmer 105, and a second connector 122 that is releasablyconnected to the signal delivery element 110. Accordingly, the signaldelivery element 110 can include a connection element that allows it tobe connected to a signal generator either directly (if it is longenough) or indirectly (if it is not). The practitioner can test theefficacy of the signal delivery element 110 in an initial position. Thepractitioner can then disconnect the cable assembly 120, reposition thesignal delivery element 110, and reapply the electrical modulation. Thisprocess can be performed iteratively until the practitioner obtains thedesired position for the signal delivery device 110. Optionally, thepractitioner may move the partially implanted signal delivery element110 without disconnecting the cable assembly 120. Further details ofsuitable cable assembly methods and associated techniques are describedin co-pending U.S. application Ser. No. 12/562,892, filed on Sep. 18,2009, and incorporated herein by reference. As will be discussed infurther detail later, particular aspects of the present disclosure canadvantageously reduce or eliminate the foregoing iterative process.

After the position of the signal delivery element 110 and appropriatesignal delivery parameters are established using the external programmer105, the patient 190 can receive therapy via signals generated by theexternal programmer 105, generally for a limited period of time. In arepresentative application, the patient 190 receives such therapy forone week. During this time, the patient wears the cable assembly 120 andthe external programmer 105 outside the body. Assuming the trial therapyis effective or, shows the promise of being effective, the practitionerthen replaces the external programmer 105 with the implanted pulsegenerator 101, and programs the pulse generator 101 with parametersselected based on the experience gained during the trial period.Optionally, the practitioner can also replace the signal deliveryelement 110. Once the implantable pulse generator 101 has beenpositioned within the patient 190, the signal delivery parametersprovided by the pulse generator 101 can still be updated remotely via awireless physician's programmer (e.g., a physician's remote) 111 and/ora wireless patient programmer 106 (e.g., a patient remote). Generally,the patient 190 has control over fewer parameters than does thepractitioner. For example, the capability of the patient programmer 106may be limited to starting and/or stopping the pulse generator 101,and/or adjusting the signal amplitude.

In any of the foregoing embodiments, the parameters in accordance withwhich the pulse generator 101 provides signals can be modulated duringportions of the therapy regimen. For example, the frequency, amplitude,pulse width and/or signal delivery location can be modulated inaccordance with a preset program, patient and/or physician inputs,and/or in a random or pseudorandom manner. Such parameter variations canbe used to address a number of potential clinical situations, includingchanges in the patient's perception of pain, changes in the preferredtarget neural population, and/or patient accommodation or habituation.

Certain aspects of the foregoing systems and methods may be simplifiedor eliminated in particular embodiments of the present disclosure. Forexample, in at least some instances, the therapeutic signals deliveredby the system can produce an effect that is much less sensitive to leadlocation and signal delivery parameters (e.g., amplitude) than areconventional stimulation systems. Accordingly, as noted above, the trialand error process (or parts of this process) for identifying a suitablelead location and associated signal delivery parameters during the leadimplant procedure can be eliminated. In addition to or in lieu of thissimplification, the post-lead implant trial period can be eliminated. Inaddition to or in lieu of the foregoing simplifications, the process ofselecting signal delivery parameters and administering the signals on along-term basis can be significantly simplified. Further aspects ofthese and other expected beneficial results are discussed in greaterdetail below.

2.0 Representative Therapy Parameters

Nevro Corporation, the assignee of the present application, hasconducted a multi-site clinical study during which multiple patientswere first treated with conventional spinal chord stimulation (SCS)techniques, and then with newly developed techniques that are disclosedfurther below. This study was followed up by a further clinical studyfocusing on the newly developed techniques, which confirmed and expandedon results obtained during the initial study. Multiple embodiments ofthe newly developed techniques, therapies and/or systems are referred toas presently disclosed techniques, therapies, and/or systems, or moregenerally as presently disclosed technologies.

2.1. Initial Comparison Study

Prior to the initial clinical study, selected patients were identifiedas suffering from primary chronic low back pain (e.g., neuropathic pain,and/or nociceptive pain, and/or other types of pain, depending upon thepatient), either alone or in combination with pain affecting otherareas, typically the patient's leg(s). In all cases, the low back painwas dominant. During the study, the patients were outfitted with twoleads, each implanted in the spinal region in a manner generally similarto that shown in FIG. 1A. One lead was implanted on one side of thespinal cord midline 189, and the other lead was implanted on the otherside of the spinal cord midline 189. FIG. 1B is a cross-sectionalillustration of the spinal cord 191 and an adjacent vertebra 195 (basedgenerally on information from Crossman and Neary, “Neuroanatomy,” 1995(published by Churchill Livingstone)), along with the locations at whichleads 110 were implanted in a representative patient. The spinal cord191 is situated between a ventrally located ventral body 196 and thedorsally located transverse process 198 and spinous process 197. ArrowsV and D identify the ventral and dorsal directions, respectively. Thespinal cord 191 itself is located within the dura mater 199, which alsosurrounds portions of the nerves exiting the spinal cord 191, includingthe dorsal roots 193 and dorsal root ganglia 194. The leads 110 werepositioned just off the spinal cord midline 189 (e.g., about 1 mm.offset) in opposing lateral directions so that the two leads 110 werespaced apart from each other by about 2 mm.

Patients with the leads 110 located as shown in FIG. 1B initially hadthe leads positioned at vertebral levels T7-T8. This location is typicalfor standard SCS treatment of low back pain because it has generallybeen the case that at lower (inferior) vertebral levels, standard SCStreatment produces undesirable side effects, and/or is less efficacious.Such side effects include unwanted muscle activation and/or pain. Oncethe leads 110 were implanted, the patients received standard SCStreatment for a period of five days. This treatment included stimulationat a frequency of less than 1500 Hz (e.g., 60-80 Hz), a pulse width of100-200 μsec, and a duty cycle of 100%. The amplitude of the signal(e.g., the current amplitude) was varied from about 3 mA to about 10 mA.The amplitude was initially established during the implant procedure.The amplitude was then changed by the patient on an as-desired basisduring the course of the study, as is typical for standard SCStherapies.

After the patient completed the standard SCS portion of the study, thepatient then received modulation in accordance with the presentlydisclosed techniques. One aspect of these techniques included moving theleads 110 inferiorly, so as to be located at vertebral levels T9, T10,T11, and/or T12. After the leads 110 were repositioned, the patientreceived therapeutic signals at a frequency of from about 3 kHz to about10 kHz. In particular cases, the therapy was applied at 8 kHz, 9 kHz or10 kHz. These frequencies are significantly higher than the frequenciesassociated with standard SCS, and accordingly, modulation at these andother representative frequencies (e.g., from about 1.5 kHz to about 100kHz) is occasionally referred to herein as high frequency modulation.The modulation was applied generally at a duty cycle of from about 50%to about 100%, with the modulation signal on for a period of from about1 msec. to about 2 seconds, and off for a period of from about 1 msec.to about 1.5 seconds. The width of the applied pulses was about 30-35μsec., and the amplitude generally varied from about 1 mA to about 4 mA(nominally about 2.5 mA). Modulation in accordance with the foregoingparameters was typically applied to the patients for a period of aboutfour days during the initial clinical study.

FIGS. 2-6A graphically illustrate summaries of the clinical resultsobtained by testing patients in accordance with the foregoingparameters. FIG. 2 is a bar chart illustrating the patients' VisualAnalog Scale (VAS) pain score for a variety of conditions. The scoresindicated in FIG. 2 are for overall pain. As noted above, these patientssuffered primarily from low back pain and accordingly, the pain scoresfor low back pain alone were approximately the same as those shown inFIG. 2. Each of the bars represents an average of the values reported bythe multiple patients involved in this portion of the study. Bars 201and 202 illustrate a baseline pain level of 8.7 for the patients withoutthe benefit of medication, and a baseline level of 6.8 with medication,respectively. After receiving a lead implant on day zero of the study,and initiating high frequency modulation in accordance with theforegoing parameters, patients reported an average pain score of about4.0, as represented by bar 203. Over the course of the next three days,(represented by bars 204-213) the patients recorded pain levels in adiary every morning, midday and evening, as indicated by thecorrespondingly labeled bars in FIG. 2. In addition, pain levels wererecorded daily by the local center research coordinator on case reportforms (CRFs) as indicated by the correspondingly labeled bars in FIG. 2.During this time period, the patients' average pain score graduallydecreased to a reported minimum level of about 2.2 (represented by bars212 and 213).

For purposes of comparison, bar 214 illustrates the pain score for thesame patients receiving standard SCS therapy earlier in the study. Bar214 indicates that the average pain value for standard SCS therapy was3.8. Unlike the results of the presently disclosed therapy, standard SCStherapy tended to produce relatively flat patient pain results over thecourse of several days. Comparing bars 213 and 214, the clinical resultsindicate that the presently disclosed therapy reduced pain in by 42%when compared with standard SCS therapy.

Other pain indices indicated generally consistent results. On theOswestry Disability Index, average scores dropped from a baseline valueof 54 to a value of 33, which is equivalent to a change from “severedisability” to “moderate disability”. Patients' global improvementscores ranked 1.9 on a scale of 1 (“very much improved”) to 7 (“verymuch worse”).

In addition to obtaining greater pain relief with the presentlydisclosed therapy than with standard SCS therapy, patients experiencedother benefits as well, described further below with reference to FIGS.3-5C. FIG. 3 is a bar chart illustrating the number of times per daythat the patients initiated modulation changes. Results are illustratedfor standard SCS therapy (bar 301) and the presently disclosed therapy(bar 302). The patient-initiated modulation changes were generallychanges in the amplitude of the applied signal, and were initiated bythe patient via an external modulator or remote, such as was describedabove with reference to FIG. 1A. Patients receiving standard SCS therapyinitiated changes to the signal delivery parameters an average of 44times per day. The initiated changes were typically triggered when thepatient changed position, activity level, and/or activity type, and thenexperienced a reduction in pain relief and/or an unpleasant,uncomfortable, painful, unwanted or unexpected sensation from thetherapeutic signal. Patients receiving the presently disclosed therapydid not change the signal delivery parameters at all, except at thepractitioners' request. In particular, the patients did not changesignal amplitude to avoid painful stimulation. Accordingly, FIG. 3indicates that the presently disclosed therapy is significantly lesssensitive to lead movement, patient position, activity level andactivity type than is standard SCS therapy.

FIG. 4 is a bar graph illustrating activity scores for patientsreceiving the presently disclosed therapy. The activity score is aquality of life score indicating generally the patients' level ofsatisfaction with the amount of activity that they are able toundertake. As indicated in FIG. 4, bar 401 identifies patients having ascore of 1.9 (e.g., poor to fair) before beginning therapy. The scoreimproved over time (bars 402-404) so that at the end of the second dayof therapy, patients reported a score of nearly 3 (corresponding to ascore of “good”). It is expected that in longer studies, the patients'score may well improve beyond the results shown in FIG. 4. Even theresults shown in FIG. 4, however, indicate a 53% improvement (comparedto baseline) in the activity score for patients receiving the presentlydisclosed therapy over a three day period. Anecdotally, patients alsoindicated that they were more active when receiving the presentlydisclosed therapy than they were when receiving standard SCS therapy.Based on anecdotal reports, it is expected that patients receivingstandard SCS therapy would experience only a 10-15% improvement inactivity score over the same period of time.

FIG. 5A is a bar chart illustrating changes in activity score forpatients receiving the presently disclosed therapy and performing sixactivities: standing, walking, climbing, sitting, riding in a car, andeating. For each of these activities, groups of bars (with individualgroups identified by reference numbers 501, 502, 503 . . . 506) indicatethat the patients' activity score generally improved over the course oftime. These results further indicate that the improvement in activitywas broad-based and not limited to a particular activity. Still further,these results indicate a significant level of improvement in eachactivity, ranging from 30% for eating to 80%-90% for standing, walkingand climbing stairs. Anecdotally, it is expected that patients receivingstandard SCS treatment would experience only about 10%-20% improvementin patient activity. Also anecdotally, the improvement in activity levelwas directly observed in at least some patients who were hunched overwhen receiving standard SCS treatment, and were unable to stand upstraight. By contrast, these patients were able to stand up straight andengage in other normal activities when receiving the presently disclosedtherapy.

The improvement experienced by the patients is not limited toimprovements in activity but also extends to relative inactivity,including sleep. For example, patients receiving standard SCS therapymay establish a signal delivery parameter at a particular level whenlying prone. When the patient rolls over while sleeping, the patient mayexperience a significant enough change in the pain reduction provided bystandard SCS treatments to cause the patient to wake. In many cases, thepatient may additionally experience pain generated by the SCS signalitself, on top of the pain the SCS signal is intended to reduce. Withthe presently disclosed techniques, by contrast, this undesirable effectcan be avoided. FIGS. 5B and 5C illustrate the average effect on sleepfor clinical patients receiving the presently disclosed therapy. FIG. 5Billustrates the reduction in patient disturbances, and FIG. 5Cillustrates the increase in number of hours slept. In other embodiments,the patient may be able to perform other tasks with reduced pain. Forexample, patients may drive without having to adjust the therapy levelprovided by the implanted device. Accordingly, the presently disclosedtherapy may be more readily used by patients in such situations and/orother situations that improve the patients' quality of life.

Based on additional patient feedback, every one of the tested patientswho received the presently disclosed therapy at the target location(e.g., who received the presently disclosed therapy without the leadmigrating significantly from its intended location) preferred thepresently disclosed therapy to standard SCS therapy. In addition,irrespective of the level of pain relief the patients received, 88% ofthe patients preferred the presently disclosed therapy to standard SCStherapy because it reduced their pain without creating paresthesia. Thisindicates that while patients may prefer paresthesia to pain, asignificant majority prefer no sensation to both pain and paresthesia.This result, obtained via the presently disclosed therapy, is notavailable with standard SCS therapies that are commonly understood torely on paresthesia (i.e., masking) to produce pain relief.

Still further, anecdotal data indicate that patients receiving thepresently disclosed therapy experienced less muscle capture than theyexperienced with standard SCS. In particular, patients reported a lackof spasms, cramps, and muscle pain, some or all of which theyexperienced when receiving standard SCS. Patients also reported nointerference with volitional muscle action, and instead indicated thatthey were able to perform motor tasks unimpeded by the presentlydisclosed therapy. Still further, patients reported no interference withother sensations, including sense of touch (e.g., detecting vibration),temperature and proprioception. In most cases, patients reported nointerference with nociceptive pain sensation. However, in some cases,patients reported an absence of incision pain (associated with theincision used to implant the signal delivery lead) or an absence ofchronic peripheral pain (associated with arthritis). Accordingly, inparticular embodiments, aspects of the currently disclosed techniquesmay be used to address nociceptive pain, including acute peripheralpain, and/or chronic peripheral pain. For example, in at least somecases, patients with low to moderate nociceptive pain received relief asa result of the foregoing therapy. Patients with more severe/chronicnociceptive pain were typically not fully responsive to the presenttherapy techniques. This result may be used in a diagnostic setting todistinguish the types of pain experienced by the patients, as will bediscussed in greater detail later.

FIG. 6A is a bar chart indicating the number of successful therapeuticoutcomes as a function of the location (indicated by vertebral level) ofthe active contacts on the leads that provided the presently disclosedtherapy. In some cases, patients obtained successful outcomes whenmodulation was provided at more than one vertebral location. Asindicated in FIG. 6A, successful outcomes were obtained over a largeaxial range (as measured in a superior-inferior direction along thespine) from vertebral bodies T9 to T12. This is a surprising result inthat it indicates that while there may be a preferred target location(e.g., around T10), the lead can be positioned at a wide variety oflocations while still producing successful results. In particular,neighboring vertebral bodies are typically spaced apart from each otherby approximately 32 millimeters (depending on specific patient anatomy),and so successful results were obtained over a broad range of fourvertebral bodies (about 128 mm.) and a narrower range of one to twovertebral bodies (about 32-64 mm.). By contrast, standard SCS datagenerally indicate that the therapy may change from effective toineffective with a shift of as little as 1 mm. in lead location. As willbe discussed in greater detail later, the flexibility and versatilityassociated with the presently disclosed therapy can produce significantbenefits for both the patient and the practitioner.

FIGS. 6B and 6C are flow diagrams illustrating methods for treatingpatients in accordance with particular embodiments of the presentdisclosure. Manufacturers or other suitable entities can provideinstructions to practitioners for executing these and other methodsdisclosed herein. Manufacturers can also program devices of thedisclosed systems to carry out at least some of these methods. FIG. 6Billustrates a method 600 that includes implanting a signal generator ina patient (block 610). The signal generator can be implanted at thepatient's lower back or other suitable location. The method 600 furtherincludes implanting a signal delivery device (e.g., a lead, paddle orother suitable device) at the patient's spinal cord region (block 620).This portion of the method can in turn include implanting the device(e.g., active contacts of the device) at a vertebral level ranging fromabout T9 to about T12 (e.g., about T9-T12, inclusive) (block 621), andat a lateral location ranging from the spinal cord midline to the DREZ,inclusive (block 622). At block 630, the method includes applying a highfrequency waveform, via the signal generator and the signal deliverydevice. In particular examples, the frequency of the signal (or at leasta portion of the signal) can be from about 1.5 kHz to about 100 kHz, orfrom about 1.5 kHz to about 50 kHz., or from about 3 kHz to about 20kHz, or from about 3 kHz to about 15 kHz, or from about 5 kHz to about15 kHz, or from about 3 kHz to about 10 kHz. The method 600 furtherincludes blocking, suppressing, inhibiting or otherwise reducing thepatient's pain, e.g., chronic low back pain (block 640). This portion ofthe method can in turn include reducing pain without unwanted sensoryeffects and/or limitations (block 641), and/or without motor effects(block 642). For example, block 641 can include reducing or eliminatingpain without reducing patient perception of other sensations, and/orwithout triggering additional pain. Block 642 can include reducing oreliminating pain without triggering muscle action and/or withoutinterfering with motor signal transmission.

FIG. 6C illustrates a method 601 that includes features in addition tothose described above with reference to FIG. 6B. For example, theprocess of applying a high frequency waveform (block 630) can includedoing so over a wide amplitude range (e.g., from less than 1 mA up toabout 8 mA in one embodiment, and up to about 6 mA and about 5 mA,respectively, in other embodiments) without creating unwanted sideeffects, such as undesirable sensations and/or motor interference (block631). In another embodiment, the process of applying a high frequencywaveform can include applying the waveform at a fixed amplitude (block632). As described further later, each of these aspects can providepatient and/or practitioner benefits.

The process of blocking, suppressing or otherwise reducing patient pain(block 640) can include doing so without creating paresthesia (block643), or in association with a deliberately generated paresthesia (block644). As noted above, clinical results indicate that most patientsprefer the absence of paresthesia to the presence of paresthesia, e.g.,because the sensation of paresthesia may change to an uncomfortable orpainful sensation when the patient changes position and/or adjusts thesignal amplitude. However, in some cases, patients may prefer thesensation of paresthesia (e.g., patients who have previously receivedSCS), and so can have the option of receiving it. Further details ofmethodologies that include combinations of paresthesia-inducingmodulation and non-paresthesia-inducing modulation are included in U.S.Provisional Application No. 61/171,790, previously incorporated hereinby reference. In other cases, paresthesia may be used by thepractitioner for site selection (e.g., to determine the location atwhich active electrodes are positioned). In addition to the above,reducing patient pain can include doing so with relative insensitivityto patient attributes that standard SCS is normally highly sensitive to(block 645). These attributes can include patient movement (block 646)and/or patient position (block 647).

2.2. Follow-on Study

Nevro Corporation, the assignee of the present application, hasconducted a follow-on study to evaluate particular parameters andresults of the therapy described above. In the follow-on study, patientsreceived implanted leads and simulators, and received therapy over aperiod of several months. This study did not include a direct comparisonwith conventional SCS techniques for each patient, though some of thepatients received conventional SCS therapy prior to receiving modulationin accordance with the present technology. Selected results aredescribed further below.

FIG. 7A is a schematic illustration of a typical lead placement usedduring the follow-on study. In this study, two leads 111 (shown as afirst lead 111 a and a second lead 111 b) were positioned generallyend-to-end to provide a modulation capability that extends over severalvertebral levels of the patients' spine. The leads 111 a, 111 b werepositioned to overlap slightly, to account for possible shifts in leadlocation. During the course of the therapy, contacts C of the two leads111 a, 111 b were activated on one lead at a time. In other words, thecontacts C of only one lead 111 were active at any one time, and signalswere not directed between the contacts C located on different leads 111.While two leads were used during the clinical study, it is expected thatin general use, a single lead can be positioned at the appropriatevertebral level. The lead can have more widely spaced contacts toachieve the same or similar effects as those described herein as will bedescribed in greater detail below with reference to FIG. 9.

The contacts C of each lead 111 a, 111 b have a width W2 ofapproximately 3 mm, and are separated from each other by a distance D1of approximately 1 mm. Accordingly, the center-to-center spacing Sbetween neighboring contacts C is approximately 4 mm. The leads 111 a,111 b were positioned at or close to the patients' spinal midline 189.Typically, one lead was positioned on one side of the midline 189, andthe other lead was positioned on the other side of the patients' midline189. During the course of the study, several significant effects wereobserved. For example, the leads 111 a, 111 b could be positioned at anyof a variety of locations within a relatively wide window W1 having anoverall width of ±3-5 mm from the midline 189 (e.g., an overall width of6-10 mm), without significantly affecting the efficacy of the treatment.In addition, patients with bilateral pain (e.g., on both sides of themidline 189) reported bilateral relief, independent of the laterallocation of the leads 110 a, 110 b. For example, patients having a leadlocated within the window W1 on one side of the midline 189 reportedpain relief on the opposite side of the midline 189. This is unlikeconventional SCS therapies, for which bilateral relief, when it isobtained at all, is generally very sensitive to any departure from astrictly midline lead location. Still further, the distance betweenneighboring active contacts was significantly greater than is typicalfor standard SCS. Practitioners were able to “skip” (e.g., deactivate)several consecutive contacts so that neighboring active contacts had acenter-to-center spacing of, for example, 20 mm, and an edge-to-edgespacing of, for example, 17 mm. In addition, patients were relativelyinsensitive to the axial location of the active contacts. For example,practitioners were able to establish the same or generally the samelevels of pain relief over a wide range of contact spacings that isexpected to extend up to two vertebral bodies (e.g., about 64 mm). Yetfurther, the practitioners obtained a similar therapeutic effect whethera given contact was identified as cathodic or anodic, as is described ingreater detail later.

For most patients in the follow-on study, the leads were implanted atthe T9-T10 vertebral locations. These patients typically experiencedprimarily low back pain prior to receiving the therapy, though someexperienced leg pain as well. Based on the results obtained during thefollow-on study and the initial study, it is expected that the overallvertebral location range for addressing low back pain is from about T9to about T12. It is further expected that within this range, modulationat T12 or T11-T12 may more effectively treat patients with both low backand leg pain. However, in some cases, patients experienced greater legpain relief at higher vertebral locations (e.g., T9-T10) and in stillfurther particular cases, modulation at T9 produced more leg pain reliefthan modulation at T10. Accordingly, within the general ranges describedabove, particular patients may have physiological characteristics orother factors that produce corresponding preferred vertebral locations.

Patients receiving treatment in the follow-on study received asquare-wave signal at a frequency of about 10 kHz. Patients receivedmodulation at a 100% duty cycle, with an initial current amplitude(bi-phasic) of about 2 mA. Patients and practitioners were able toadjust the signal amplitude, typically up to about 5 mA. At any of theforegoing levels, the signal pulses are expected to be suprathreshold,meaning that they can trigger an action potential in the target neuralpopulation, independent of any intrinsic neural activity at the targetneural population.

Patients in the follow-on study were evaluated periodically after themodulation system 100 was implanted and activated. The VAS scoresreported by these patients after 30 days of receiving treatment averagedabout 1.0, indicating that the trend discussed above with respect toFIG. 2 continued for some period of time. At least some of thesepatients reported an increase in the VAS score up to level of about2.25. It is expected that this increase resulted from the patients'increased activity level. Accordingly, it is not believed that thisincrease indicates a reduction in the efficacy of the treatment, butrather, indicates an effective therapy that allows patients to engage inactivities they otherwise would not.

FIG. 7B illustrates overall Oswestry scores for patients engaging in avariety of activities and receiving modulation in accordance with thefollow-on study protocol. A score of 100 corresponds to a completelydisabled condition, and a score of 0 corresponds to no disability. Thesescores indicate a general improvement over time, for example, consistentwith and in fact improved over results from in the initial study. Inaddition, several patients reported no longer needing or using canes orwheelchairs after receiving therapy in accordance with the foregoingembodiments.

Results from the follow-on study confirm a relative insensitivity of thetherapeutic effectiveness of the treatment to changes in currentamplitude. In particular, patients typically received modulation at alevel of from about 2.0 mA to about 3.5 mA. In most cases, patients didnot report significant changes in pain reduction when they changed theamplitude of the applied signal. Patients were in several cases able toincrease the current amplitude up to a level of about 5 mA beforereporting undesirable side effects. In addition, the side effects beganto take place in a gradual, rather than a sudden, manner. Anecdotalfeedback from some patients indicated that at high amplitudes (e.g.,above 5 mA) the treatment efficacy began to fall off, independent of theonset of any undesirable side effects. It is further expected thatpatients can receive effective therapy at current amplitudes of lessthan 2 mA. This expectation is based at least in part on data indicatingthat reducing the duty cycle (e.g., to 70%) did not reduce efficacy.

The results of the follow-on study also indicated that most patients(e.g., approximately 80% of the patients) experienced at leastsatisfactory pain reduction without changing any aspect of the signaldelivery parameters (e.g., the number and/or location of activecontacts, and/or the current amplitude), once the system was implantedand activated. A small subset of the patients (e.g., about 20%)benefited from an increased current amplitude when engaging inparticular activities, and/or benefited from a lower current amplitudewhen sleeping. For these patients, increasing the signal amplitude whileengaging in activity produced a greater degree of pain relief, andreducing the amplitude at night reduced the likelihood ofover-stimulation, while at the same time saving power. In arepresentative example, patients selected from between two suchprograms: a “strong” program which provided signals at a relatively highcurrent amplitude (e.g., from about 1 mA to about 6 mA), and a “weak”program which provided signals at a lower current amplitude (e.g., fromabout 0.1 mA to about 3 mA).

Another observed effect during the follow-on study was that patientsvoluntarily reduced their intake of opioids and/or other painmedications that they had been receiving to address pain prior toreceiving modulation in accordance with the present technology. Thepatients' voluntary drug intake reduction is expected to be a directresult of the decreased need for the drugs, which is in turn a directresult of the modulation provided in accordance with the presenttechnology. However, due to the addictive nature of opioids, the easewith which patients voluntarily gave up the use of opioids wassurprising. Therefore, it is also expected that for at least somepatients, the present technology, in addition to reducing pain, acted toreduce the chemical dependency on these drugs. Accordingly, it isfurther expected that in at least some embodiments, therapeutictechniques in accordance with the present disclosure may be used toreduce or eliminate patient chemical dependencies, independent ofwhether the patients also have and/or are treated for low back pain.

Patients entering the follow-on study typically experienced neuropathicpain, nociceptive pain, or a combination of neuropathic pain andnociceptive pain. Neuropathic pain refers generally to pain resultingfrom a dysfunction in the neural mechanism for reporting pain, which canproduce a sensation of pain without an external neural trigger.Nociceptive pain refers generally to pain that is properly sensed by thepatient as being triggered by a particular mechanical or other physicaleffect (e.g., a slipped disc, a damaged muscle, or a damaged bone). Ingeneral, neuropathic pain is consistent, and nociceptive painfluctuates, e.g., with patient position or activity. In at least someembodiments, treatment in accordance with the present technology appearsto more effectively address neuropathic pain than nociceptive pain. Forexample, patients who reported low levels of pain fluctuation beforeentering treatment (indicating predominantly neuropathic pain), receivedgreater pain relief during treatment than patients whose pain fluctuatedsignificantly. In two particular cases, the therapy did not prove to beeffective, and it is believe that this resulted from a mechanical issuewith the patients' back anatomy, which identified the patients as bettercandidates for surgery than for the present therapy. Accordingly, inaddition to addressing neuropathic pain and (in at least some cases),nociceptive pain, techniques in accordance with the present technologymay also act as a screening tool to identify patients who sufferprimarily from nociceptive pain rather than neuropathic pain. Forexample, the practitioner can make such an identification based at leastin part on feedback from the patient corresponding to the existenceand/or amount (including amount of fluctuation) of pain reduction whenreceiving signals in accordance with the present technology. As a resultof using this diagnostic technique, these patients can be directed tosurgical or other procedures that can directly address the nociceptivepain. In particular, patients may receive signals in accordance with thepresent technology and, if these patients are unresponsive, may besuitable candidates for surgical intervention. Of course, if thepatients are responsive, they can continue to receive signals inaccordance with the present technology as therapy

3.0 Mechanisms of Action

FIG. 8 is a schematic diagram (based on Linderoth and Foreman,“Mechanisms of Spinal Cord Stimulation in Painful Syndromes: Role ofAnimal Models,” Pain Medicine, Vol. 51, 2006) illustrating an expectedmechanism of action for standard SCS treatment, along with potentialmechanisms of action for therapy provided in accordance with embodimentsof the present technology. When a peripheral nerve is injured, it isbelieved that the Aδ and C nociceptors provide an increased level ofexcitatory transmitters to second order neurons at the dorsal horn ofthe spinal cord. Standard SCS therapy, represented by arrow 701, isexpected to have two effects. One effect is an orthodromic effecttransmitted along the dorsal column to the patient's brain and perceivedas paresthesia. The other is an antidromic effect that excites theinterneuron pool, which in turn inhibits inputs to the second orderneurons.

One potential mechanism of action for the presently disclosed therapy isrepresented by arrow 710, and includes producing an incompleteconduction block (e.g., an incomplete block of afferent and/or efferentsignal transmission) at the dorsal root level. This block may occur atthe dorsal column, dorsal horn, and/or dorsal root entry zone, inaddition to or in lieu of the dorsal root. In any of these cases, theconduction block is selective to and/or preferentially affects thesmaller Aδ and/or C fibers and is expected to produce a decrease inexcitatory inputs to the second order neurons, thus producing a decreasein pain signals supplied along the spinal thalamic tract.

Another potential mechanism of action (represented by arrow 720 in FIG.8) includes more profoundly activating the interneuron pool and thusincreasing the inhibition of inputs into the second order neurons. Thiscan, in effect, potentially desensitize the second order neurons andconvert them closer to a normal state before the effects of the chronicpain associated signals have an effect on the patient.

Still another potential mechanism of action relates to the sensitivityof neurons in patients suffering from chronic pain. In such patients, itis believed that the pain-transmitting neurons may be in a different,hypersensitive state compared to the same neurons in people who do notexperience chronic pain, resulting in highly sensitized cells that areon a “hair trigger” and fire more frequently and at different patternswith a lower threshold of stimulation than those cells of people who donot experience chronic pain. As a result, the brain receives asignificantly increased volume of action potentials at significantlyaltered transmission patterns. Accordingly, a potential mechanism ofaction by which the presently disclosed therapies may operate is byreducing this hypersensitivity by restoring or moving the “baseline” ofthe neural cells in chronic pain patients toward the normal baseline andfiring frequency of non-chronic pain patients. This effect can in turnreduce the sensation of pain in this patient population withoutaffecting other neural transmissions (for example, touch, heat, etc.).

The foregoing mechanisms of action are identified here as possiblemechanisms of action that may account for the foregoing clinicalresults. In particular, these mechanisms of action may explain thesurprising result that pain signals transmitted by the small, slow Aδand C fibers may be inhibited without affecting signal transmissionalong the larger, faster Aβ fibers. This is contrary to the typicalresults obtained via standard SCS treatments, during which modulationsignals generally affect Aβ fibers at low amplitudes, and do not affectAδ and C fibers until the signal amplitude is so high as to create painor other unwanted effects transmitted by the Aβ fibers. However, aspectsof the present disclosure need not be directly tied to such mechanisms.In addition, aspects of both the two foregoing proposed mechanisms mayin combination account for the observed results in some embodiments, andin other embodiments, other mechanisms may account for the observedresults, either alone or in combination with either one of the twoforegoing mechanisms. One such mechanism includes an increased abilityof high frequency modulation (compared to standard SCS stimulation) topenetrate through the cerebral spinal fluid (CSF) around the spinalcord. Another such mechanism is the expected reduction in impedancepresented by the patient's tissue to high frequencies, as compared tostandard SCS frequencies. Still another such mechanism is the ability ofhigh frequency signal to elicit an asynchronous neural response, asdisclosed in greater detail in pending U.S. application Ser. No.12/362,244, filed on Jan. 29, 2009 and incorporated herein by reference.Although the higher frequencies associated with the presently disclosedtechniques may initially appear to require more power than conventionalSCS techniques, the signal amplitude may be reduced when compared toconventional SCS values (due to improved signal penetration) and/or theduty cycle may be reduced (due to persistence effects described later).Accordingly, the presently disclosed techniques can result in a netpower savings when compared with standard SCS techniques.

4.0 Expected Benefits Associated With Certain Embodiments

Certain of the foregoing embodiments can produce one or more of avariety of advantages, for the patient and/or the practitioner, whencompared with standard SCS therapies. Some of these benefits weredescribed above. For example, the patient can receive effective painrelief without patient-detectable disruptions to normal sensory andmotor signals along the spinal cord. In particular embodiments, whilethe therapy may create some effect on normal motor and/or sensorysignals, the effect is below a level that the patient can reliablydetect intrinsically, e.g., without the aid of external assistance viainstruments or other devices. Accordingly, the patient's levels of motorsignaling and other sensory signaling (other than signaling associatedwith the target pain) can be maintained at pre-treatment levels. Forexample, as described above, the patient can experience a significantpain reduction that is largely independent of the patient's movement andposition. In particular, the patient can assume a variety of positionsand/or undertake a variety of movements associated with activities ofdaily living and/or other activities, without the need to adjust theparameters in accordance with which the therapy is applied to thepatient (e.g., the signal amplitude). This result can greatly simplifythe patient's life and reduce the effort required by the patient toexperience pain relief while engaging in a variety of activities. Thisresult can also provide an improved lifestyle for patients whoexperience pain during sleep, as discussed above with reference to FIGS.5B and 5C.

Even for patients who receive a therapeutic benefit from changes insignal amplitude, the foregoing therapy can provide advantages. Forexample, such patients can choose from a limited number of programs(e.g., two or three) each with a different amplitude and/or other signaldelivery parameter, to address some or all of the patient's pain. In onesuch example, the patient activates one program before sleeping andanother after waking. In another such example, the patient activates oneprogram before sleeping, a second program after waking, and a thirdprogram before engaging in particular activities that would otherwisecause pain. This reduced set of patient options can greatly simplify thepatient's ability to easily manage pain, without reducing (and in fact,increasing) the circumstances under which the therapy effectivelyaddresses pain. In any embodiments that include multiple programs, thepatient's workload can be further reduced by automatically detecting achange in patient circumstance, and automatically identifying anddelivering the appropriate therapy regimen. Additional details of suchtechniques and associated systems are disclosed in co-pending U.S.application Ser. No. 12/703,683, previously incorporated herein byreference.

Another benefit observed during the clinical studies described above isthat when the patient does experience a change in the therapy level, itis a gradual change. This is unlike typical changes associated withconventional SCS therapies. With conventional SCS therapies, if apatient changes position and/or changes an amplitude setting, thepatient can experience a sudden onset of pain, often described bypatients as unbearable. By contrast, patients in the clinical studiesdescribed above, when treated with the presently disclosed therapy,reported a gradual onset of pain when signal amplitude was increasedbeyond a threshold level, and/or when the patient changed position, withthe pain described as gradually becoming uncomfortable. One patientdescribed a sensation akin to a cramp coming on, but never fullydeveloping. This significant difference in patient response to changesin signal delivery parameters can allow the patient to more freelychange signal delivery parameters and/or posture when desired, withoutfear of creating an immediately painful effect.

Another observation from the clinical studies described above is thatthe amplitude “window” between the onset of effective therapy and theonset of pain or discomfort is relatively broad, and in particular,broader than it is for standard SCS treatment. For example, duringstandard SCS treatment, the patient typically experiences a painreduction at a particular amplitude, and begins experiencing pain fromthe therapeutic signal (which may have a sudden onset, as describedabove) at from about 1.2 to about 1.6 times that amplitude. Thiscorresponds to an average dynamic range of about 1.4. In addition,patients receiving standard SCS stimulation typically wish to receivethe stimulation at close to the pain onset level because the therapy isoften most effective at that level. Accordingly, patient preferences mayfurther reduce the effective dynamic range. By contrast, therapy inaccordance with the presently disclosed technology resulted in patientsobtaining pain relief at 1 mA or less, and not encountering pain ormuscle capture until the applied signal had an amplitude of 4 mA, and insome cases up to about 5 mA, 6 mA, or 8 mA, corresponding to a muchlarger dynamic range (e.g., larger than 1.6 or 60% in some embodiments,or larger than 100% in other embodiments). Even at the forgoingamplitude levels, the pain experienced by the patients was significantlyless than that associated with standard SCS pain onset. An expectedadvantage of this result is that the patient and practitioner can havesignificantly wider latitude in selecting an appropriate therapyamplitude with the presently disclosed methodology than with standardSCS methodologies. For example, the practitioner can increase the signalamplitude in an effort to affect more (e.g., deeper) fibers at thespinal cord, without triggering unwanted side effects. The existence ofa wider amplitude window may also contribute to the relativeinsensitivity of the presently disclosed therapy to changes in patientposture and/or activity. For example, if the relative position betweenthe implanted lead and the target neural population changes as thepatient moves, the effective strength of the signal when it reaches thetarget neural population may also change. When the target neuralpopulation is insensitive to a wider range of signal strengths, thiseffect can in turn allow greater patient range of motion withouttriggering undesirable side effects.

Although the presently disclosed therapies may allow the practitioner toprovide modulation over a broader range of amplitudes, in at least somecases, the practitioner may not need to use the entire range. Forexample, as described above, the instances in which the patient may needto adjust the therapy may be significantly reduced when compared withstandard SCS therapy because the presently disclosed therapy isrelatively insensitive to patient position, posture and activity level.In addition to or in lieu of the foregoing effect, the amplitude of thesignals applied in accordance with the presently disclosed techniquesmay be lower than the amplitude associated with standard SCS because thepresently disclosed techniques may target neurons that are closer to thesurface of the spinal cord. For example, it is believed that the nervefibers associated with low back pain enter the spinal cord between T9and T12 (inclusive), and are thus close to the spinal cord surface atthese vertebral locations. Accordingly, the strength of the therapeuticsignal (e.g., the current amplitude) can be modest because the signalneed not penetrate through a significant depth of spinal cord tissue tohave the intended effect. Such low amplitude signals can have a reduced(or zero) tendency for triggering side effects, such as unwanted sensoryand/or motor responses. Such low amplitude signals can also reduce thepower required by the implanted pulse generator, and can thereforeextend the battery life and the associated time between rechargingand/or replacing the battery.

Yet another expected benefit of providing therapy in accordance with theforegoing parameters is that the practitioner need not implant the leadwith the same level of precision as is typically required for standardSCS lead placement. For example, while the foregoing results wereidentified for patients having two leads (one positioned on either sideof the spinal cord midline), it is expected that patients will receivethe same or generally similar pain relief with only a single lead placedat the midline. Accordingly, the practitioner may need to implant onlyone lead, rather than two. It is still further expected that the patientmay receive pain relief on one side of the body when the lead ispositioned offset from the spinal cord midline in the oppositedirection. Thus, even if the patient has bilateral pain, e.g., with painworse on one side than the other, the patient's pain can be addressedwith a single implanted lead. Still further, it is expected that thelead position can vary laterally from the anatomical and/orphysiological spinal cord midline to a position 3-5 mm. away from thespinal cord midline (e.g., out to the dorsal root entry zone or DREZ).The foregoing identifiers of the midline may differ, but the expectationis that the foregoing range is effective for both anatomical andphysiological identifications of the midline, e.g., as a result of therobust nature of the present therapy. Yet further, it is expected thatthe lead (or more particularly, the active contact or contacts on thelead) can be positioned at any of a variety of axial locations in arange of about T9-T12 in one embodiment, and a range of one to twovertebral bodies within T9-T12 in another embodiment, while stillproviding effective treatment. Accordingly, the practitioner's selectedimplant site need not be identified or located as precisely as it is forstandard SCS procedures (axially and/or laterally), while stillproducing significant patient benefits. In particular, the practitionercan locate the active contacts within the foregoing ranges withoutadjusting the contact positions in an effort to increase treatmentefficacy and/or patient comfort. In addition, in particular embodiments,contacts at the foregoing locations can be the only active contactsdelivering therapy to the patient. The foregoing features, alone or incombination, can reduce the amount of time required to implant the lead,and can give the practitioner greater flexibility when implanting thelead. For example, if the patient has scar tissue or another impedimentat a preferred implant site, the practitioner can locate the leadelsewhere and still obtain beneficial results.

Still another expected benefit, which can result from the foregoingobserved insensitivities to lead placement and signal amplitude, is thatthe need for conducting a mapping procedure at the time the lead isimplanted may be significantly reduced or eliminated. This is anadvantage for both the patient and the practitioner because it reducesthe amount of time and effort required to establish an effective therapyregimen. In particular, standard SCS therapy typically requires that thepractitioner adjust the position of the lead and the amplitude of thesignals delivered by the lead, while the patient is in the operatingroom reporting whether or not pain reduction is achieved. Because thepresently disclosed techniques are relatively insensitive to leadposition and amplitude, the mapping process can be eliminated entirely.Instead, the practitioner can place the lead at a selected vertebrallocation (e.g., about T9-T12) and apply the signal at a pre-selectedamplitude (e.g., 1 to 2 mA), with a significantly reduced or eliminatedtrial-and-error optimization process (for a contact selection and/oramplitude selection), and then release the patient. In addition to or inlieu of the foregoing effect, the practitioner can, in at least someembodiments, provide effective therapy to the patient with a simplebipole arrangement of electrodes, as opposed to a tripole or other morecomplex arrangement that is used in existing systems to steer orotherwise direct therapeutic signals. In light of the foregoingeffect(s), it is expected that the time required to complete a patientlead implant procedure and select signal delivery parameters can bereduced by a factor of two or more, in particular embodiments. As aresult, the practitioner can treat more patients per day, and thepatients can more quickly engage in activities without pain.

The foregoing effect(s) can extend not only to the mapping procedureconducted at the practitioner's facility, but also to the subsequenttrial period. In particular, patients receiving standard SCS treatmenttypically spend a week after receiving a lead implant during which theyadjust the amplitude applied to the lead in an attempt to establishsuitable amplitudes for any of a variety of patient positions andpatient activities. Because embodiments of the presently disclosedtherapy are relatively insensitive to patient position and activitylevel, the need for this trial and error period can be reduced oreliminated.

Still another expected benefit associated with embodiments of thepresently disclosed treatment is that the treatment may be lesssusceptible to patient habituation. In particular, it is expected thatin at least some cases, the high frequency signal applied to the patientcan produce an asynchronous neural response, as is disclosed inco-pending U.S. application Ser. No. 12/362,244, previously incorporatedherein by reference. The asynchronous response may be less likely toproduce habituation than a synchronous response, which can result fromlower frequency modulation.

Yet another feature of embodiments of the foregoing therapy is that thetherapy can be applied without distinguishing between anodic contactsand cathodic contacts. As described in greater detail later, thisfeature can simplify the process of establishing a therapy regimen forthe patient. In addition, due to the high frequency of the waveform, theadjacent tissue may perceive the waveform as a pseudo steady statesignal. As a result of either or both of the foregoing effects, tissueadjacent both electrodes may be beneficially affected. This is unlikestandard SCS waveforms for which one electrode is consistently cathodicand another is consistently anodic.

In any of the foregoing embodiments, aspects of the therapy provided tothe patient may be varied within or outside the parameters used duringthe clinical testing described above, while still obtaining beneficialresults for patients suffering from chronic low back pain. For example,the location of the lead body (and in particular, the lead bodyelectrodes or contacts) can be varied over the significant lateraland/or axial ranges described above. Other characteristics of theapplied signal can also be varied. For example, as described above, thesignal can be delivered at a frequency of from about 1.5 kHz to about100 kHz, and in particular embodiments, from about 1.5 kHz to about 50kHz. In more particular embodiments, the signal can be provided atfrequencies of from about 3 kHz to about 20 kHz, or from about 3 kHz toabout 15 kHz, or from about 5 kHz to about 15 kHz, or from about 3 kHzto about 10 kHz. The amplitude of the signal can range from about 0.1 mAto about 20 mA in a particular embodiment, and in further particularembodiments, can range from about 0.5 mA to about 10 mA, or about 0.5 mAto about 4 mA, or about 0.5 mA to about 2.5 mA. The amplitude of theapplied signal can be ramped up and/or down. In particular embodiments,the amplitude can be increased or set at an initial level to establish atherapeutic effect, and then reduced to a lower level to save powerwithout forsaking efficacy, as is disclosed in pending U.S. applicationSer. No. 12/264,536, filed Nov. 4, 2008, and incorporated herein byreference. In particular embodiments, the signal amplitude refers to theelectrical current level, e.g., for current-controlled systems. In otherembodiments, the signal amplitude can refer to the electrical voltagelevel, e.g., for voltage-controlled systems. The pulse width (e.g., forjust the cathodic phase of the pulses) can vary from about 10microseconds to about 333 microseconds. In further particularembodiments, the pulse width can range from about 25 microseconds toabout 166 microseconds, or from about 33 microseconds to about 100microseconds, or from about 50 microseconds to about 166 microseconds.The specific values selected for the foregoing parameters may vary frompatient to patient and/or from indication to indication and/or on thebasis of the selected vertebral location. In addition, the methodologymay make use of other parameters, in addition to or in lieu of thosedescribed above, to monitor and/or control patient therapy. For example,in cases for which the pulse generator includes a constant voltagearrangement rather than a constant current arrangement, the currentvalues described above may be replaced with corresponding voltagevalues.

In at least some embodiments, it is expected that the foregoingamplitudes will be suprathreshold. It is also expected that, in at leastsome embodiments, the neural response to the foregoing signals will beasynchronous, as described above. Accordingly, the frequency of thesignal can be selected to be higher (e.g., between two and ten timeshigher) than the refractory period of the target neurons at thepatient's spinal cord, which in at least some embodiments is expected toproduce an asynchronous response.

Patients can receive multiple signals in accordance with still furtherembodiments of the disclosure. For example, patients can receive two ormore signals, each with different signal delivery parameters. In oneparticular example, the signals are interleaved with each other. Forinstance, the patient can receive 5 kHz pulses interleaved with 10 kHzpulses. In other embodiments, patients can receive sequential “packets”of pulses at different frequencies, with each packet having a durationof less than one second, several seconds, several minutes, or longerdepending upon the particular patient and indication.

In still further embodiments, the duty cycle may be varied from the50%-100% range of values described above, as can the lengths of theon/off periods. For example, it has been observed that patients can havetherapeutic effects (e.g., pain reduction) that persist for significantperiods after the modulation has been halted. In particular examples,the beneficial effects can persist for 10-20 minutes in some cases, andup to an hour in others and up to a day or more in still further cases.Accordingly, the simulator can be programmed to halt modulation forperiods of up to an hour, with appropriate allowances for the timenecessary to re-start the beneficial effects. This arrangement cansignificantly reduce system power consumption, compared to systems withhigher duty cycles, and compared to systems that have shorter on/offperiods.

5.0 Representative Lead Configurations

FIG. 9 is a partially schematic illustration of a lead 910 having firstand second contacts C1, C2 positioned to deliver modulation signals inaccordance with particular embodiments of the disclosure. The contactsare accordingly positioned to contact the patient's tissue whenimplanted. The lead 910 can include at least two first contacts C1 andat least two second contacts C2 to support bipolar modulation signalsvia each contact grouping. In one aspect of this embodiment, the lead910 can be elongated along a major or lead axis A, with the contacts C1,C2 spaced equally from the major axis A. In general, the term elongatedrefers to a lead or other signal delivery element having a length (e.g.,along the spinal cord) greater than its width. The lead 910 can have anoverall length L (over which active contacts are positioned) that islonger than that of typical leads. In particular, the length L can besufficient to position first contacts C1 at one or more vertebrallocations (including associated neural populations), and position thesecond contacts C2 at another vertebral location (including associatedneural populations) that is spaced apart from the first and that issuperior the first. For example, the first contacts C1 may be positionedat vertebral levels T9-T12 to treat low back pain, and the secondcontacts C2 may be positioned at superior vertebral locations (e.g.,cervical locations) to treat arm pain. Representative lead lengths arefrom about 30 cm to about 150 cm, and in particular embodiments, fromabout 40 cm to about 50 cm. Pulses may be applied to both groups ofcontacts in accordance with several different arrangements. For examplepulses provided to one group may be interleaved with pulses applied tothe other, or the same signal may be rapidly switched from one group tothe other. In other embodiments, the signals applied to individualcontacts, pairs of contacts, and/or contacts in different groups may bemultiplexed in other manners. In any of these embodiments, each of thecontacts C1, C2 can have an appropriately selected surface area, e.g.,in the range of from about 3 mm² to about 25 mm², and in particularembodiments, from about 8 mm² to about 15 mm². Individual contacts on agiven lead can have different surface area values, within the foregoingranges, than neighboring or other contacts of the lead, with valuesselected depending upon features including the vertebral location of theindividual contact.

Another aspect of an embodiment of the lead 910 shown in FIG. 9 is thatthe first contacts C1 can have a significantly wider spacing than istypically associated with standard SCS contacts. For example, the firstcontacts C1 can be spaced apart (e.g., closest edge to closest edge) bya first distance S1 that is greater than a corresponding second distanceS2 between immediately neighboring second contacts C2. In arepresentative embodiment, the first distance S1 can range from about 3mm up to a distance that corresponds to one-half of a vertebral body,one vertebral body, or two vertebral bodies (e.g., about 16 mm, 32 mm,or 64 mm, respectively). In another particular embodiment, the firstdistance S1 can be from about 5 mm to about 15 mm. This increasedspacing can reduce the complexity of the lead 910, and can still provideeffective treatment to the patient because, as discussed above, theeffectiveness of the presently disclosed therapy is relativelyinsensitive to the axial location of the signal delivery contacts. Thesecond contacts C2 can have a similar wide spacing when used to applyhigh frequency modulation in accordance with the presently disclosedmethodologies. However, in another embodiment, different portions of thelead 910 can have contacts that are spaced apart by different distances.For example, if the patient receives high frequency pain suppressiontreatment via the first contacts C1 at a first vertebral location, thepatient can optionally receive low frequency (e.g., 1500 Hz or less, or1200 Hz or less), paresthesia-inducing signals at the second vertebrallocation via the second contacts C2 that are spaced apart by a distanceS2. The distance S2 can be smaller than the distance S1 and, inparticular embodiments, can be typical of contact spacings for standardSCS treatment (e.g., 4 mm spacings), as these contacts may be used forproviding such treatment. Accordingly, the first contacts C1 can delivermodulation in accordance with different signal delivery parameters thanthose associated with the second contacts C2. In still furtherembodiments, the inferior first contacts C1 can have the close spacingS2, and the superior second contacts C2 can have the wide spacing S1,depending upon patient indications and/or preferences. In still furtherembodiments, as noted above, contacts at both the inferior and superiorlocations can have the wide spacing, e.g., to support high frequencymodulation at multiple locations along the spinal cord. In otherembodiments, the lead 910 can include other arrangements of differentcontact spacings, depending upon the particular patient and indication.For example, the widths of the second contacts C2 (and/or the firstcontacts C1) can be a greater fraction of the spacing betweenneighboring contacts than is represented schematically in FIG. 9. Thedistance S1 between neighboring first contacts C1 can be less than anentire vertebral body (e.g., 5 mm or 16 mm) or greater than onevertebral body while still achieving benefits associated with increasedspacing, e.g., reduced complexity. The lead 910 can have all contactsspaced equally (e.g., by up to about two vertebral bodies), or thecontacts can have different spacings, as described above. Two or morefirst contacts C1 can apply modulation at one vertebral level (e.g., T9)while two or more additional first contacts C1 can provide modulation atthe same or a different frequency at a different vertebral level (e.g.,T10).

In some cases, it may be desirable to adjust the distance between theinferior contacts C1 and the superior contacts C2. For example, the lead910 can have a coil arrangement (like a telephone cord) or otherlength-adjusting feature that allows the practitioner to selectivelyvary the distance between the sets of contacts. In a particular aspectof this arrangement, the coiled portion of the lead can be locatedbetween the first contacts C1 and the second contacts C2. For example,in an embodiment shown in FIG. 10A, the lead 910 can include a proximalportion 910 a carrying the first contacts C1, a distal portion 910 ccarrying the second contacts C2, and an intermediate portion 910 bhaving a pre-shaped, variable-length strain relief feature, for example,a sinusoidally-shaped or a helically-shaped feature. The lead 910 alsoincludes a stylet channel or lumen 915 extending through the lead 910from the proximal portion 910 a to the distal portion 910 c.

Referring next to FIG. 10B, the practitioner inserts a stylet 916 intothe stylet lumen 915, which straightens the lead 910 for implantation.The practitioner then inserts the lead 910 into the patient, via thestylet 916, until the distal portion 910 c and the associated secondcontacts C2 are at the desired location. The practitioner then securesthe distal portion 910 c relative to the patient with a distal leaddevice 917 c. The distal lead device 917 c can include any of a varietyof suitable remotely deployable structures for securing the lead,including, but not limited to an expandable balloon.

Referring next to FIG. 10C, the practitioner can partially or completelyremove the stylet 916 and allow the properties of the lead 910 (e.g.,the natural tendency of the intermediate portion 910 b to assume itsinitial shape) to draw the proximal portion 910 a toward the distalportion 910 c. When the proximal portion 910 a has the desired spacingrelative to the distal portion 910 c, the practitioner can secure theproximal portion 910 a relative to the patient with a proximal leaddevice 917 a (e.g., a suture or other lead anchor). In this manner, thepractitioner can select an appropriate spacing between the firstcontacts C1 at the proximal portion 910 a and the second contacts C2 atdistal portion 910 c that provides effective treatment at multiplepatient locations along the spine.

FIG. 11A is an enlarged view of the proximal portion 910 a of the lead910, illustrating an internal arrangement in accordance with aparticular embodiment of the disclosure. FIG. 11B is a cross-sectionalview of the lead 910 taken substantially along line 11B-11B of FIG. 11A.Referring now to FIG. 11B, the lead 910 can include multiple conductors921 arranged within an outer insulation element 918, for example, aplastic sleeve. In a particular embodiment, the conductors 921 caninclude a central conductor 921 a. In another embodiment, the centralconductor 921 a can be eliminated and replaced with the stylet lumen 915described above. In any of these embodiments, each individual conductor921 can include multiple conductor strands 919 (e.g., a multifilararrangement) surrounded by an individual conductor insulation element920. During manufacture, selected portions of the outer insulation 918and the individual conductor insulation elements 920 can be removed,thus exposing individual conductors 921 at selected positions along thelength of the lead 910. These exposed portions can themselves functionas contacts, and accordingly can provide modulation to the patient. Inanother embodiment, ring (or cylinder) contacts are attached to theexposed portions, e.g., by crimping or welding. The manufacturer cancustomize the lead 910 by spacing the removed sections of the outerinsulation element 918 and the conductor insulation elements 920 in aparticular manner. For example, the manufacturer can use a stencil orother arrangement to guide the removal process, which can include, butis not limited to, an ablative process. This arrangement allows the sameoverall configuration of the lead 910 to be used for a variety ofapplications and patients without major changes. In another aspect ofthis embodiment, each of the conductors 921 can extend parallel to theothers along the major axis of the lead 910 within the outer insulation918, as opposed to a braided or coiled arrangement. In addition, each ofthe conductor strands 919 of an individual conductor element 920 canextend parallel to its neighbors, also without spiraling. It is expectedthat these features, alone or in combination, wilt increase theflexibility of the overall lead 910, allowing it to be inserted with agreater level of versatility and/or into a greater variety of patientanatomies then conventional leads.

FIG. 11C is a partially schematic, enlarged illustration of the proximalportion 910 a shown in FIG. 11A. One expected advantage of themultifilar cable described above with reference to FIG. 11B is that theimpedance of each of the conductors 921 can be reduced when compared toconventional coil conductors. As a result, the diameter of theconductors 921 can be reduced and the overall diameter of the lead 910can also be reduced. One result of advantageously reducing the leaddiameter is that the contacts C1 may have a greater length in order toprovide the required surface area needed for effective modulation. Ifthe contacts C1 are formed from exposed portions of the conductors 921,this is not expected to present an issue. If the contacts C1 are ring orcylindrical contacts, then in particular embodiments, the length of thecontact may become so great that it inhibits the practitioner's abilityto readily maneuver the lead 910 during patient insertion. One approachto addressing this potential issue is to divide a particular contact C1into multiple sub-contacts, shown in FIG. 11C as six sub-contacts C1a-C1 f. In this embodiment, each of the individual sub-contacts C1 a-C1f can be connected to the same conductor 921 shown in FIG. 11B.Accordingly, the group of sub-contacts connected to a given conductor921 can operate essentially as one long contact, without inhibiting theflexibility of the lead 910.

As noted above, one feature of the foregoing arrangements is that theycan be easy to design and manufacture. For example, the manufacturer canuse different stencils to provide different contact spacings, dependingupon specific patient applications. In addition to or in lieu of theforegoing effect, the foregoing arrangement can provide for greatermaneuverability and facilitate the implantation process by eliminatingring electrodes and/or other rigid contacts, or dividing the contactsinto subcontacts. In other embodiments, other arrangements can be usedto provide contact flexibility. For example, the contacts can be formedfrom a conductive silicone, e.g., silicone impregnated with a suitableloading of conductive material, such as platinum, iridium or anothernoble metal.

Yet another feature of an embodiment of the lead shown in FIG. 9 is thata patient can receive effective therapy with just a single bipolar pairof active contacts. If more than one pair of contacts is active, eachpair of contacts can receive the identical waveform, so that activecontacts can be shorted to each other. In another embodiment, theimplanted pulse generator (not visible in FIG. 9) can serve as a returnelectrode. For example, the pulse generator can include a housing thatserves as the return electrode, or the pulse generator can otherwisecarry a return electrode that has a fixed position relative to the pulsegenerator. Accordingly, the modulation provided by the active contactscan be unipolar modulation, as opposed to the more typical bipolarstimulation associated with standard SCS treatments.

6.0 Representative Programmer Configurations

The robust characteristics of the presently disclosed therapy techniquesmay enable other aspects of the overall system described above withreference to FIGS. 1A-B to be simplified. For example, the patientremote and the physician programmer can be simplified significantlybecause the need to change signal delivery parameters can be reducedsignificantly or eliminated entirely. In particular, it is expected thatin certain embodiments, once the lead is implanted, the patient canreceive effective therapy while assuming a wide range of positions andengaging in a wide range of activities, without having to change thesignal amplitude or other signal delivery parameters. As a result, thepatient remote need not include any programming functions, but caninstead include a simple on/off function (e.g., an on/off button orswitch). The patient remote may also include an indicator (e.g., alight) that identifies when the pulse generator is active. This featuremay be particularly useful in connection with the presently disclosedtherapies because the patient will typically not feel a paresthesia,unless the system is configured and programmed to deliberately produceparesthesia in addition to the therapy signal. In particularembodiments, the physician programmer can be simplified in a similarmanner, though in some cases, it may be desirable to maintain at leastsome level of programming ability at the physician programmer. Such acapability can allow the physician to select different contacts and/orother signal delivery parameters in the rare instances when the leadmigrates or when the patient undergoes physiological changes (e.g.,scarring) or lifestyle changes (e.g., new activities) that are sosignificant they require a change in the active contact(s) and/or othersignal delivery parameters. FIGS. 12A-13E illustrate representativedevices and associated methodologies that reflect one or more of theforegoing features in accordance with particular embodiments of thepresent disclosure.

FIG. 12A is a partially schematic illustration of a remote controldevice 1200 (e.g., a patient remote) configured in accordance with anembodiment of the disclosure. The patient remote 1200 can be operated bya patient during the course of therapy, e.g., generally as describedabove with reference to FIG. 1A. In a particular embodiment shown inFIG. 12A, the patient remote 1200 includes a wireless transmitter andonly a single input device 1201. The wireless transmitter establishes acommunication link 1205 with an implanted pulse generator (e.g., thepulse generator 101 described above with reference to FIG. 1A). A linkindicator 1203 indicates whether the patient remote 1200 has establishedthe communication link 1205 with the pulse generator, which in turnenables directive signals provided by the input device 1201 to betransmitted to the pulse generator.

In a further particular aspect of this embodiment, the single inputdevice 1201 controls only two states of the associated implanted pulsegenerator. For example, the input device 1201 can control only whetherthe pulse generator is “on” (e.g., enabled to provide modulating signalsto the patient) or “off” (e.g., disabled from providing modulatingsignals to the patient). In yet a further particular embodiment, thesingle input device 1201 can be limited so as to (a) allow the pulsegenerator to be on so long as the input device 1201 is not activated,and to (b) shut the pulse generator down if the input device 1201 isactivated. In this embodiment, the practitioner initially activates thepulse generator, and the patient can shut it off (e.g., under specificconditions, such as an emergency). The practitioner's input is thenrequired to re-activate the pulse generator. A power indicator 1202(e.g., an LED or other visual indicator, audio indicator, or other typeof indicator) identifies whether the input device 1201 has placed theassociated pulse generator in an on state or an off state. This feedbackfeature may be of particular value to a patient receivingnon-paresthesia-inducing therapy, because the patient may notimmediately sense such therapy otherwise. The input device 1201 caninclude a push button, touch pad, or other suitable component. In aparticular embodiment, the input device 1201 can send a differentdirective signal to the pulse generator, depending upon whether theinput signal is intended to turn the pulse generator on or off. Inanother embodiment, the input device 1201 can send the same signal tothe pulse generator, and the pulse generator simply toggles between anon state and an off state with each new input received via the inputdevice 1201. In any of these embodiments, the patient remote 1201 can besized and shaped to be easily held and operated with one hand.

FIG. 12B is a partially schematic illustration of a patient remote 1200configured in accordance with another embodiment of the disclosure. Inthis embodiment, the input device 1201 can direct the associatedimplanted pulse generator to be in one of at most two or possibly more(e.g., three) alternate states. For example, the implanted pulsegenerator can be configured to deliver signals to the patient inaccordance with a most two different signal delivery programs. Byactivating the input device 1201, the patient can toggle between a firstprogram and a second program. Each program can have associated with it acorresponding program indicator 1204 a, 1204 b, and the active programcan be indicated by a different appearance of the correspondingindicator. For example, the program indicators 1204 a, 1204 b caninclude lights, LEDs or other devices that are active (e.g.,illuminated) when the associated program is active, and inactive whenthe associated program is inactive. In representative embodiments, thetwo programs can be sleep/awake programs or normally active patient/veryactive patient programs. In these and other embodiments, the differencebetween programs can be limited to current amplitude differences (asopposed to other differences, e.g., frequency differences and activecontact differences). The patient remote 1200 can also be used tocontrol whether the implanted pulse generator is on or off, with an offstate indicated when neither program indicator 1204 a, 1204 b is active.As discussed above with reference to FIG. 12A, the patient remote 1200can issue different directive signals depending upon the desired targetstate at the implanted pulse generator, or the patient remote 1200 candirect the same signal to the implanted pulse generator, and theimplanted pulse generator can sequentially step through the states(e.g., off, program 1, program 2, off, etc.) with the arrival of eachnew directive signal.

One feature of the embodiments described above with reference to FIGS.12A and 12B is that the patient remote 1200 can include a limitedfunction input device 1201, e.g., an input device that is prohibitedfrom carrying out certain actions. In particular, the patient remote1200 shown in FIG. 12A can only change the state of the correspondingimplanted pulse generator between an on state and an off state, and thepatient remote 1200 shown in FIG. 12B can only change the state of thecorresponding implanted pulse generator between an off state, a firstprogram, and a second program. Notably, the patient remote 1200 shown inFIG. 12A does not have control over the amplitude, frequency, and/orother signal delivery parameters in accordance with which the modulatingsignal is provided to the patient. The patient remote 1200 shown in FIG.12B has limited control over these features, in that the differentprograms will typically include different signal delivery parameters.However, the patient remote 1200 does not have capability to controleach of the signal delivery parameters independently, or outside theconfines of the selectable programs set by the practitioner.

One advantage of the foregoing arrangement is that it can simplify thepatient's life by reducing the patient's involvement with controllingthe therapy provided by the electrical signals. In this embodiment,reduced control is not a disadvantage for the patient, but insteadcapitalizes on the robust nature of the therapy described above. Forexample, the robust nature of the therapy can reduce or eliminate theneed for the patient to control signal amplitude, delivery locationand/or other parameters without impacting the efficacy of the therapy.Another advantage associated with the foregoing features is that thepractitioner can more easily track the therapy delivered to the patient.For example, the patient remote 1200 can store information identifyingwhen the implanted pulse generator is activated and, if the patient hasenabled multiple programs, which program is active. With fewer variablesto control, the data are expected to be simpler to understand and easierto make use of.

In other embodiments, the overall system can operate in other manners toachieve at least some of the foregoing results. For example, the pulsegenerator can be configured to respond only to certain requests, or notrespond to particular requests from a patient remote. In a particularexample, the pulse generator can be configured to not respond torequests from a patient remote for a change in amplitude, program, oractive contact selection. One application for this approach is that itallows existing patient remotes to be used in the limited-functionmanner described above.

FIGS. 13A-13E illustrate devices and associated methodologies that thepractitioner can use to control the therapy provided to the patient. Ingeneral, these devices and methodologies allow the practitioner morecontrol over the therapy than is typically granted to the patient. Thesefeatures and methodologies can be implemented on a device that istemporarily hardwired directly to the lead (e.g., in the manner of theexternal programmer 105 described above with reference to FIG. 1A) orvia a wireless link to an implanted pulse generator (e.g., in the mannerof the physician's programmer 111, also described above with referenceto FIG. 1A). The patient remote 1200 and the practitioner's controllercan each include different security keys, codes, or authorizationarrangements that are automatically transmitted to and interpreted bythe controlled device (e.g., the implanted pulse generator).Accordingly, the controlled device can be controlled by either thepatient remote (e.g., in a first mode) or the practitioner's controller(e.g., in a second mode) as appropriate.

FIG. 13A schematically illustrates a practitioner's controller 1310having a display medium 1312 (e.g., an LCD, LED array, or other suitablemedium) and one or more input devices 1311 that are used to inputinformation displayed at the display medium 1312. The practitioner'scontroller 1310 can also include an internal memory 1313 and processor1314 (and/or other computer/machine readable media) that store andexecute programs and/or instructions associated with establishing andpresenting signal delivery parameters at the display medium 1312. If thecontroller 1310 is connected directly to a lead or other signal deliverydevice, then it also includes an internal pulse generator for generatingthe modulation signal. If the controller 1310 is wirelessly connected toan implanted pulse generator, then it can control the manner in whichsignals are generated by the implanted pulse generator. Aspects ofdisplays presented at the display medium 1312 are described in furtherdetail below with reference to FIGS. 13B-13E.

FIG. 13B illustrates a representation of a display 1320 that may bepresented at the display medium 1312 shown in FIG. 13A. The display 1320can include a two-dimensional, graphical layout, with a vertical axialscale 1321 identifying axial locations along the patient's spine (e.g.,from T8 to T12) and a lateral amplitude scale 1322 identifying thecurrent amplitude (e.g., in mA) with which a therapeutic signal isdelivered to the patient. The display 1320 also includes a therapylocation identifier 1326 indicating where along the axial scale 1321 themodulation signal is applied, and an available amplitude window 1323that indicates the range of current amplitudes the practitioner hasaccess to. An amplitude identifier 1324 indicates the present amplitudelevel. Accordingly, the practitioner can move the therapy locationidentifier 1326 up and down along the axial scale 1321 (e.g., using adrag and drop routine or other suitable arrangement), and can adjust theamplitude of the signal by moving the amplitude identifier 1324 back andforth (e.g., also using a drag and drop or other suitable arrangement).

The display 1320 also includes one or more pain score identifiers 1327(three of which are shown in FIG. 13B as first, second, and third painscore identifiers 1327 a, 1327 b, 1327 c, respectively). The pain scoreidentifiers 1327 can identify numerical VAS scores (or other suitableindex values) as a function of amplitude and axial location along thespine. The scores can be for the particular patient presently receivingtherapeutic modulation, or for other relevant patients or patientpopulations. For example, the pain score identifiers 1327 can reflectdata for a patient population having symptoms or indications similar tothose experienced by the present patient. Accordingly, the practitionercan view historical pain scores for a representative patient or patientpopulation in the same manner and on the same display as are displayedthe location and amplitude of the patient presently receivingtherapeutic modulation. This can aid the practitioner in selecting anappropriate axial location and amplitude for the present patient. Forexample, the practitioner can locate the amplitude and axial location ofthe modulation at or proximate to the pain score identifier 1327 withthe lowest value (e.g., pain score identifier 1327 a). An advantage ofthis arrangement is that it presents historical information andadjustable patient parameters together in an easy-to-view andeasy-to-manipulate format.

FIG. 13B illustrates a single lead extending from about vertebral levelT8 to about vertebral level T12. In other embodiments, the patient mayhave multiple leads implanted along the spine. For example, referringnow to FIG. 13C, the display 1320 presents a first lead identifier 1325a corresponding to a first lead and a second, inferiorly located leadidentifier 1325 b corresponding to a second lead. Using the leadidentifiers 1325 a, 1325 b as guides, the practitioner can manipulatethe location and amplitude of the modulation provided to the patient, inthe manner generally described above with reference to FIG. 13B. In theregion where the two leads overlap, the practitioner can drag orotherwise move the therapy location identifier 1326 laterally from onelead to another to select the lead that will apply the modulationsignal. If the practitioner drags the therapy location identifier 1326above or below the axial extent of a particular lead, the program canautomatically shift the therapy location identifier to 1326 to theadjacent lead, assuming the adjacent lead has the appropriate axialextent. In any of these embodiments, the program can automaticallyselect the contacts on the lead that are closest to the therapy locationidentifier 1326. Further aspects of this feature are described ingreater detail below with reference to FIGS. 13D and 13E.

Referring now to FIG. 13D, the detailed display 1320 described abovewith reference to FIGS. 13B and 13C has been simplified and made part ofan overall display 1320 a. The overall display 1320 a can include astatus identifier 1330 (e.g., identifying the patient, device, andbattery state), a program options indicator 1328 (e.g., identifyingavailable programs), a lead position summary 1329, and a signal deliveryparameter identifier 1333. The overall display 1320 a can also includecontact identifiers 1331 for each implanted lead. In the embodimentshown in FIG. 13D, the patient has two implanted leads and accordinglytwo corresponding sets of contact identifiers 1331 a, 1331 b. Next toeach contact identifier set 1331 a, 1331 b is a corresponding programidentifier 1332 a, 1332 b which identifies an available program (e.g.,program “P1”). The therapy location indicator 1326 appears along theprogram identifier 1332 a to indicate the location at which the therapyis provided in association with that program. In the particularembodiment shown in FIG. 13D, the patient receives therapy centeredapproximately at vertebral location T9.5, via the left/superior lead andno therapy via the right/inferior lead.

As indicated above, the program can automatically select appropriatesignal delivery contacts depending upon the location at which thepractitioner places the therapy location identifier 1326. For example,as shown in FIG. 13D, the practitioner has moved the therapy locationidentifier 1326 to the illustrated location, and the program hasautomatically selected contacts “3” and “5” to deliver modulation overan area extending at least between these contacts. One feature of thisarrangement is that the practitioner need not select which contacts areactive. Instead, the practitioner can select the desired vertebrallocation (e.g., based on the pain score indicators 1327) and allow theprogram to select the appropriate contacts. Another feature of thisarrangement is that the practitioner need not select which of the activecontacts is anodic or cathodic. As used herein, the cathodic contactrefers to the contact that receives a negative or polarizing pulse atthe outset of a pulse train in accordance with which the modulation isprovided. As discussed above, it is believed that the presentlydisclosed therapy is insensitive or relatively insensitive to whichcontact in a bipolar pair of contacts is anodic or cathodic.Accordingly, the practitioner need not make this selection, whichsimplifies the practitioner's task of establishing program parametersfor the patient. In particular, the practitioner controller 1310 can beprohibited from accepting user inputs for cathode/anode selection.Instead, the program executed by the practitioner's controller 1310 (orby the implanted pulse generator with which it communicates) canautomatically select which contact is anodic and which is cathodicwithout user input, in accordance with any of a variety suitablealgorithms. For example, the program can select the superior contact tobe cathodic, and the inferior contact to be anodic. In otherembodiments, this relationship can be reversed.

In any of the foregoing embodiments described above with reference toFIG. 13D, the therapy location identifier 1326 can be highlighted orotherwise differentiated when the practitioner has active control overthe signal delivery parameters associated with the therapy provided atthat location. For example, as shown in FIG. 13D, the therapy locationidentifier 1326 is brightly displayed, indicating to the practitionerthat the associated signal delivery parameters may be controlled bymanipulating the signal delivery parameter identifiers 1333. Theseidentifiers can include pulse identifiers 1335, and amplitudeidentifiers 1334. The amplitude identifiers 1334 can include a minimumamplitude 1336, a maximum amplitude 1337, a starting amplitude 1338, anamplitude step identifier 1339, and a present amplitude identifier 1340.The practitioner can select the amplitude step and then adjust theamplitude between the minimum value and the maximum value, with thepresent value indicated by the present amplitude identifier 1340.

One feature of the arrangement shown in FIG. 13D is that the minimumamplitude 1336 can be a non-zero value set by the practitioner or by themanufacturer. This is unlike typical SCS controllers, which generallyallow the practitioner or the patient to adjust the amplitude down tozero. The present therapy however, often does not provide an immediatelydetectable sensation (e.g., paresthesia) that indicates to the patientthat the therapy is operating. Accordingly, establishing a minimumamplitude level can prevent the patient or the practitioner frominadvertently selecting an amplitude that is too low to provide therapy,which may not be detected by the patient for some time. In a particularembodiment shown in FIG. 13D, the minimum amplitude is set at 2 mA. Asdiscussed above, the minimum amplitude may have lower values (e.g., 1 mAor 0.5 mA) depending upon factors including patient-specific factorsand/or indication-specific factors.

FIG. 13E is a partially schematic illustration of the display 1320 a,showing information relating to multiple leads, multiple programs, andmultiple therapy location indicators. In particular, FIG. 13Eillustrates the first contact identifier set 1331 a associated with afirst lead, and the second contact identifier set 1331 b associated witha second lead. Two available programs (“P1” and “P2”) are indicated foreach lead by program identifiers 1332 a 1, 1332 a 2 for the first lead,and program identifiers 1332 b 1, 1332 b 2 for the second lead. In thisparticular arrangement, the practitioner has selected modulationlocations for both programs 1 and 2 at the first lead (as shown by firstand second therapy location indicators 1326 a 1, 1326 a 2), and for onlyprogram 2 (as shown by a third therapy location indicator 1326 b 2) atthe second lead. The signal delivery parameters presented by the signaldelivery parameter identifiers 1333 are associated with the therapyprovided at the first lead under program P2, as identified by the secondlocation indicator 1326 a 2, which is highlighted in FIG. 13E. The otherselected therapy location indicators 1326 a 1 and 1326 b 2 are shown ingray scale. Accordingly, the practitioner can readily identify whichprogram and therapy location the signal delivery parameter identifiers1333 correspond to.

Another feature shown in FIG. 13E is that the practitioner can, ifdesired, override the default contact selection procedure carried out bythe program. For example, the program automatically selected the therapyareas to extend over three contacts for programs P1 and P2 at the firstlead. In a particular embodiment, this can be the default selectionprocess. For program P2 at the second lead, the practitioner has changedthe length of the therapy location identifier 1326 b 2 so that itextends over four contacts (contacts 11-14). In other embodiments, thepractitioner can select the therapy area to extend over other lengths,shorter or longer than those shown in FIG. 3E. In general, the programcan select the two contacts positioned at the superior and inferiorextremes of the therapy area to be the active contacts.

7.0 Representative Modulation Locations and Indications

Many of the embodiments described above were described in the context oftreating chronic, neuropathic low back pain with modulation signalsapplied to the lower thoracic vertebrae (T9-T12). In other embodiments,modulation signals having parameters (e.g., frequency, pulse width,amplitude, and/or duty cycle) generally similar to those described abovecan be applied to other patient locations to address other indications.For example, while the foregoing methodologies included applyingmodulation at lateral locations ranging from the spinal cord midline tothe DREZ, in other embodiments, the modulation may be applied to theforamen region, laterally outward from the DREZ. In other embodiments,the modulation may be applied to other spinal levels of the patient. Forexample, modulation may be applied to the sacral region and moreparticularly, the “horse tail” region at which the sacral nerves enterthe sacrum. Urinary incontinence and fecal incontinence representexample indications that are expected to be treatable with modulationapplied at this location. In other embodiments, the modulation may beapplied to other thoracic vertebrae. For example, modulation may beapplied to thoracic vertebrae above T9. In a particular embodiment,modulation may be applied to the T3-T6 region to treat angina.Modulation can be applied to high thoracic vertebrae to treat painassociated with shingles. Modulation may be applied to the cervicalvertebrae to address chronic regional pain syndrome and/or total bodypain, and may be used to replace neck surgery. Suitable cervicallocations include vertebral levels C3-C7, inclusive. In otherembodiments, modulation may be applied to the occipital nerves, forexample, to address migraine headaches.

As described above, modulation in accordance with the foregoingparameters may also be applied to treat acute and/or chronic nociceptivepain. For example, modulation in accordance with these parameters can beused during surgery to supplement and/or replace anesthetics (e.g., aspinal tap). Such applications may be used for tumor removal, kneesurgery, and/or other surgical techniques. Similar techniques may beused with an implanted device to address post-operative pain, and canavoid the need for topical lidocaine. In still further embodiments,modulation in accordance with the foregoing parameters can be used toaddress other peripheral nerves. For example, modulation can be applieddirectly to peripheral nerves to address phantom limb pain.

From the foregoing, it will be appreciated that specific embodiments ofthe disclosure have been described herein for purposes of illustration,but that various modifications may be made without deviating from thedisclosure. For example, the specific parameter ranges and indicationsdescribed above may be different in further embodiments. As describedabove, the practitioner can avoid the use of certain procedures, (e.g.,mapping, trial periods and/or current steering), but in otherembodiments, such procedures may be used in particular instances. Thelead described above with reference to FIGS. 9-11C can have more thantwo groups of contacts, and/or can have other contact spacings in otherembodiments. In some embodiments, as described above, the signalamplitude applied to the patient can be constant. In other embodiments,the amplitude can vary in a preselected manner, e.g., via rampingup/down, and/or cycling among multiple amplitudes. The signal deliveryelements can have an epidural location, as discussed above with regardto FIG. 1B, and in other embodiments, can have an extradural location.In particular embodiments described above, signals having the foregoingcharacteristics are expected to provide therapeutic benefits forpatients having low back pain and/or leg pain, when modulation isapplied at vertebral levels from about T9 to about T12. In at least someother embodiments, it is believed that this range can extend from aboutT5 to about L1.

Certain aspects of the disclosure described in the context of particularembodiments may be combined or eliminated in other embodiments. Forexample, as described above, the trial period, operating room mappingprocess, and/or external modulator may be eliminated or simplified inparticular embodiments. Therapies directed to particular indications maybe combined in still further embodiments. Further, while advantagesassociated with certain embodiments have been described in the contextof those embodiments, other embodiments may also exhibit suchadvantages, and not all embodiments need necessarily exhibit suchadvantages to fall within the scope of the present disclosure.Accordingly, the present disclosure and associated technology canencompass other embodiments not expressly shown or described herein.

1. A patient therapy system, comprising: a patient-implantable signaldelivery device; a patient-implantable pulse generator electricallyconnected to the signal delivery device, the pulse generator beingprogrammed with instructions for delivering a modulation signal at afrequency of from about 3 kHz to about 50 kHz; and a remote controlhaving only a single input device that is wirelessly coupleable to thepulse generator, the input device being operable to produce no more thantwo states at the pulse generator: a first state in which the pulsegenerator is activated to deliver the modulation signal, and a secondstate in which the pulse generator is prohibited from delivering themodulation signal.
 2. The system of claim 1 wherein (a) the remotecontrol is prohibited from issuing a directive to change an amplitude ofthe modulation signal, or (b) the pulse generator is prohibited fromresponding to a directive received from the remote control to change anamplitude of the modulation signal, or (c) both (a) and (b).
 3. Thesystem of claim 1 wherein (a) the remote control is prohibited fromissuing a directive to change an automated program in accordance withwhich the modulation signal is delivered, or (b) the pulse generator isprohibited from responding to a directive received from the remotecontrol to change an automated program in accordance with which themodulation signal is delivered, or (c) both (a) and (b).
 4. The systemof claim 1 wherein the signal delivery device includes multipleelectrical contacts, and wherein (a) the remote control is prohibitedfrom issuing a directive to change which contacts receive the modulationsignal, or (b) the pulse generator is prohibited from responding to adirective received from the remote control to change which contactsreceive the modulation signal, or (c) both (a) and (b).
 5. The system ofclaim 1 wherein the input device includes a push-button.
 6. The systemof claim 1 wherein the remote control includes an indicator identifyingwhich state the pulse generator is in.
 7. The system of claim 1 whereinthe remote control includes an indicator identifying whether or not awireless link is established with the pulse generator.
 8. The system ofclaim 1 in which the remote control is a first remote control, andwherein the system further comprises a second remote control, the secondremote control having at least one input device that is wirelesslycoupleable to the pulse generator, the input device of the second remotecontrol being actuatable to produce multiple active states at the pulsegenerator, with the pulse generator directing the modulation signal inaccordance with different signal delivery parameters for correspondingdifferent active states.
 9. The system of claim 1 wherein the signaldelivery device includes an elongated spinal lead body.
 10. The systemof claim 1 wherein the single input device is operable to change thepulse generator from the first state to the second state, but not thesecond state to the first state.
 11. The system of claim 1 wherein thesingle input device is operable to change the pulse generator back andforth between the first and second states.
 12. A patient therapy system,comprising: a remote control that is wirelessly coupleable to animplantable pulse generator, the remote control including: a wirelesscommunication device; and a single input device coupled to the wirelesscommunication device to transmit an instruction signal, the single inputdevice being the only input device of the remote control operativelycoupled to the wireless communication device to transmit an instructionsignal, the single input device being operable to produce at most twostates at the pulse generator: a first state in which the pulsegenerator is activated to deliver a modulation signal to a patient, anda second state in which the pulse generator is prohibited fromdelivering the modulation signal.
 13. The therapy system of claim 12 inwhich the remote control is a first remote control, and wherein thesystem further comprises a second remote control, the second remotecontrol having at least one input device that is wirelessly coupleablewith the pulse generator, the input device of the second remote controlbeing actuatable to produce greater than two states at the pulsegenerator, and wherein the states include multiple active states, withindividual active states directing the modulation signal in accordancewith corresponding different signal delivery parameters.
 14. The therapysystem of claim 13 wherein the first and second remote controls havedifferent access security features.
 15. The system of claim 12, furthercomprising the implantable pulse generator, and wherein the implantedpulse generator is programmed with instructions for delivering amodulation signal at a frequency of from about 3 kHz to about 50 kHz.16. The therapy system of claim 12, further comprising a signal deliverydevice coupled to the implantable pulse generator, and wherein thesignal delivery device includes an elongated spinal lead body.
 17. Apatient therapy system, comprising: an implantable pulse generator thatis wirelessly coupleable to a remote control device, the pulse generatorincluding: a wireless receiver; a machine-readable medium operativelycoupled to the wireless receiver and having instructions for deliveringan electrical modulation signal to a patient in accordance with a firstmode and a second mode, wherein: under the first mode, the pulsegenerator is limited to starting and halting delivery of the electricalmodulation signal in response to inputs received at the first wirelessreceiver, and wherein under the second mode, the pulse generator iscontrollable to start, halt and modify delivery of the electricalmodulation signal, in response to inputs received at the wirelessreceiver; and wherein the pulse generator changes between the first andsecond modes based upon an authorization signal received via thewireless receiver.
 18. The system of claim 17, further comprising: afirst remote control having instructions for transmitting a firstauthorization signal to the pulse generator to allow operation of thepulse generator in the first mode; and a second remote control havinginstructions for transmitting a second authorization signal to the pulsegenerator to allow operation of the pulse generator in the second mode.19. The system of claim 17 wherein the machine-readable medium isprogrammed with instructions for delivering the electrical modulationsignal at a frequency of from about 3 kHz to about 50 kHz.
 20. Thesystem of claim 17 wherein the machine-readable medium is programmedwith instructions for delivering the electrical modulation signal at afrequency of from about 5 kHz to about 15 kHz.
 21. The system of claim17, further comprising an implantable signal delivery device coupleableto the pulse generator, and wherein the signal delivery device includesan elongated spinal lead.
 22. A method for making a patient system,comprising: programming a patient-implantable pulse generator with aninstruction set for delivering an electrical therapy signal to apatient, the pulse generator having a wireless receiver to receivesignals from a remote control; and (a) providing the remote control witha pulse generator control function limited to activating and halting theelectrical therapy signal; or (b) providing the pulse generator with aresponse function to the remote control that is limited to activatingand halting the electrical therapy signal; or (c) both (a) and (b). 23.The method of claim 22 wherein programming the pulse generator includesprogramming the pulse generator with an instruction set for deliveringthe electrical therapy signal at a frequency of from about 3 kHz toabout 50 kHz.
 24. The method of claim 22 wherein programming the pulsegenerator includes programming the pulse generator with an instructionset for delivering the electrical therapy signal at a frequency of fromabout 5 kHz to about 15 kHz.
 25. The method of claim 22 in which theremote control is a first remote control, and wherein the method furthercomprises providing a second remote control with a control function thatincludes producing multiple active states at the pulse generator, withthe pulse generator directing the modulation signal in accordance withdifferent signal delivery parameters for corresponding different activestates.
 26. A method for operating a patient therapy system, comprising:controlling a signal delivery device implanted in a patient, via awireless remote control positioned external to the patient, whereincontrolling the signal delivery device via the remote control is limitedto controlling only whether the signal delivery device delivers signalsto the patient at a frequency of from about 3 kHz to about 50 kHz, ordoes not deliver signals to the patient.
 27. The method of claim 26wherein controlling a signal delivery device includes controlling asignal delivery device implanted proximate to the patient's spine,within a foramen of at least one of the patient's vertebra.
 28. Themethod of claim 26 wherein controlling a signal delivery device includescontrolling a signal delivery device without changing an amplitude ofthe modulation signal.
 29. The method of claim 26 wherein controlling asignal delivery device includes controlling a signal delivery devicewithout changing an automated program in accordance with which themodulation signal is delivered.
 30. The system of claim 26 wherein thesignal delivery device includes multiple electrical contacts, andwherein controlling a signal delivery device includes controlling asignal delivery device without changing which contacts the modulationsignal is delivered to. 31-82. (canceled)